Sodium Hydroxide → 3-Methyl-1,6-diazaspiro[3,5]nonane-1-carboxylic acid 1-benzyl ester

HRID 1912384Notes

Reaction equation

HRID 1912384 reaction equation
C(OC([N:8]1[CH2:27][CH2:26][CH2:25][C:10]2([N:13]([C:14]([O:16][CH2:17][C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)=[O:15])[CH2:12][CH:11]2[CH3:24])[CH2:9]1)=O)(C)(C)C.FC(F)(F)C(O)=O.C(Cl)(Cl)Cl.[OH-].[Na+]>C(Cl)(Cl)Cl>[CH2:17]([O:16][C:14]([N:13]1[C:10]2([CH2:25][CH2:26][CH2:27][NH:8][CH2:9]2)[CH:11]([CH3:24])[CH2:12]1)=[O:15])[C:18]1[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=1

Participants

5

Reactant 3

HCID 14798Sodium HydroxideHCID 19978452Chloroform trifluoroacetic acidHCID 582933041-Benzyl6-tert-butyl3-methyl-1,6-diazaspiro[3.5]nonane-1,6-dicarboxylate

Product 1

HCID 582933243-Methyl-1,6-diazaspiro[3,5]nonane-1-carboxylic acid 1-benzyl esterYield 54.2%

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent

Procedure

To a solution of an optically-active compound of 3-methyl-1,6-diazaspiro[3,5]nonane-1,6-dicarboxylic acid 1-benzyl ester 6-tert-butyl ester (5.54 g) in chloroform (83 ml) cooled to 4° C. was added a solution of trifluoroacetic acid/chloroform (28 ml/55 ml), and the mixture was warmed to room temperature and stirred for additional 2 hours. The reaction mixture was cooled to 4° C., and thereto was added 4M aqueous sodium hydroxide solution (90 ml). The mixture was basified to be pH 9 to 10, and extracted with chloroform/methanol (4/1, 60 ml×2) twice. The combined organic layer was sequentially washed with 5% aqueous sodium bicarbonate solution, 10% aqueous sodium chloride solution, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (eluent: chloroform/methanol/28% ammonia water=90/10/1) to give the titled compound (2.20 g).

Workup

  1. temperatureThe reaction mixture was cooled to 4° C.
  2. extractionextracted with chloroform/methanol (4/1, 60 ml×2) twice
  3. washThe combined organic layer was sequentially washed with 5% aqueous sodium bicarbonate solution, 10% aqueous sodium chloride solution
  4. dry with materialdried over anhydrous magnesium sulfate
  5. concentrationconcentrated under reduced pressure
  6. customThe resulting residue was purified by silica gel column chromatography (eluent: chloroform/methanol/28% ammonia water=90/10/1)

Sources & evidence

ORD record
ord-57e5587a8d844abdb9d47e034f26beae
Source dataset
uspto-grants-2013_12
Patent number
US08609647B2

Reaction notes

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